Stroke remains the leading cause of chronic disability in the U.S., and more than half of stroke survivors have persistent impairment of arm function despite receiving conventional therapy. In these stroke survivors, a significant cause of impaired arm movement is abnormal co-activation between muscles that normally do not activate together. The long-term goal of this research is to develop a new therapy for stroke using an inexpensive, easily portable device to improve motor function by decoupling abnormally co-activating muscles. This therapy, a myoelectric computer interface (MCI), maps electrical muscle activity onto movements of a cursor in a computer game. This provides direct, detailed feedback about the co-activation of a pair of muscles to the user. Our preliminary results suggest that training with the MCI allows stroke survivors to greatly reduce abnormal co-activation in the targeted arm muscle pair and may also improve function. The objective of this proposal is to determine how to optimize translation of the decoupled muscle activations into functional improvement. We seek to improve motor function in chronic stroke survivors by even more than in our preliminary studies, which assessed isometric MCI training of a single muscle pair. We will test the effects of two different doses of training on motor function. We will also assess the extent to which individual muscles can be decoupled during movement, which is a more functionally relevant condition than isometric activation. The specific aims of the proposal are to 1) determine the extent to which isometric MCI training of multiple muscle pairs improves function, and 2) determine the extent to which movement-based MCI training of multiple muscle pairs improves function. The proposed research is innovative because it applies fundamental insight about abnormal co-activation after stroke to develop a novel treatment modality that will be inexpensive and portable. In addition, it tests the fundamental ability of an injured central nervous system to regain precise control over specific pairs of muscles. The ability to regain precise control of individual muscles is important because it should improve the ability to transfer the learned behavior to functional tasks. This therapy will broadly impact the field sinc it can enable use by a wide range of stroke survivors. This includes those with severe motor impairments, who are those most in need of new therapies. Achieving our objective will be significant because we expect it to lead to development of an effective treatment for impaired movement after stroke and set the stage for initial clinical trials of the therapy. We estimate tht this therapy could benefit at least 1 million stroke survivors in the U.S. alone.